title: Integrating sequence, expression and interaction data to determine condition-specific miRNA regulation.
abstract: BACKGROUND
  MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression post-transcriptionally. MiRNAs were shown to play an important role in development and disease, and accurately determining the networks regulated by these miRNAs in a specific condition is of great interest. Early work on miRNA target prediction has focused on using static sequence information. More recently, researchers have combined sequence and expression data to identify such targets in various conditions.
  
  
  RESULTS
  We developed the Protein Interaction-based MicroRNA Modules (PIMiM), a regression-based probabilistic method that integrates sequence, expression and interaction data to identify modules of mRNAs controlled by small sets of miRNAs. We formulate an optimization problem and develop a learning framework to determine the module regulation and membership. Applying PIMiM to cancer data, we show that by adding protein interaction data and modeling cooperative regulation of mRNAs by a small number of miRNAs, PIMiM can accurately identify both miRNA and their targets improving on previous methods. We next used PIMiM to jointly analyze a number of different types of cancers and identified both common and cancer-type-specific miRNA regulators.
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Machine Learning Department, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
authors.forename: Hai-Son
authors.initials: HS
authors.lastname: Le
authors.forename: Ziv
authors.initials: Z
authors.lastname: Bar-Joseph
mesh_terms: D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D015233:Models, Statistical; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism; D025941:Protein Interaction Mapping; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D017423:Sequence Analysis, RNA
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger